More than 107,000 Americans died of drug overdoses last year, setting another tragic record in the nation's escalating overdose epidemic, the Centers for Disease Control and Prevention estimated Wednesday.

The provisional 2021 total translates to roughly one U.S. overdose death every 5 minutes. It marked a 15% increase from the previous record, set the year before. The CDC reviews death certificates and then makes an estimate to account for delayed and incomplete reporting.

Dr. Nora Volkow, director of the National Institute on Drug Abuse, called the latest numbers “truly staggering.”

U.S. overdose deaths have risen most years for more than two decades. The increase began in the 1990s with overdoses involving opioid painkillers, followed by waves of deaths led by other opioids like heroin and - most recently - illicit fentanyl.

Last year, overdoses involving fentanyl and other synthetic opioids surpassed 71,000, up 23% from the year before. There also was a 23% increase in deaths involving cocaine and a 34% increase in deaths involving meth and other stimulants.

Overdose deaths are often attributed to more than one drug. Some people take multiple drugs and inexpensive fentanyl has been increasingly cut into other drugs, often without the buyers' knowledge, officials say.

“The net effect is that we have many more people, including those who use drugs occasionally and even adolescents, exposed to these potent substances that can cause someone to overdose even with a relatively small exposure,” Volkow said in a statement.

Experts say the COVID-19 pandemic has exacerbated the problem as lockdowns and other restrictions isolated those with drug addictions and made treatment harder to get.

Overdose death trends are geographically uneven. Alaska saw a 75% increase in 2021 - the largest jump of any state. In Hawaii, overdose deaths fell by 2%.